Materials leading to improved dental composites and dental composites made therefrom

ABSTRACT

This invention relates to composite materials for restorative dentistry. More particularly, it relates to new components for dental composites, which impart an attractive combination of good mechanical properties and low shrinkage.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority under 35 U.S.C. §119 from U.S.Provisional Application Ser. No. 60/680,610, filed May 13, 2005.

FIELD OF THE INVENTION

This invention relates to composite materials for restorative dentistry.More particularly, it relates to new components for dental compositesthat impart an attractive combination of good mechanical properties andlow shrinkage.

BACKGROUND OF THE INVENTION

In recent years, composite materials comprising highly filled polymershave become commonly used for dental restorations. Current compositematerials contain crosslinking acrylates or methacrylates, inorganicfillers such as glass or quartz, and a photoinitiator system suitablefor curing by visible light. Typical methacrylate materials include2,2′-bis[4-(2-hydroxy-3-methacryloyloxypropyl)phenyl]propane(“Bis-GMA”); ethoxylated Bisphenol A dimethacrylate (“EBPDMA”);1,6-bis-[2-methacryloyloxyethoxycarbonylamino]-2,4,4-trimethylhexane(“UDMA”); dodecanediol dimethacrylate (“D₃MA”); and triethyleneglycoldimethacrylate (“TEGDMA”). The structural formulae for these are shownbelow.

Dental composite materials offer a distinct cosmetic advantage overtraditional metal amalgam. However, they do not offer the longevity ofamalgam in dental fillings. The primary reason for failure is excessiveshrinkage during photopolymerization in the tooth cavity, which cancause leakage and bacterial reentry. Another reason is they haveinadequate strength and toughness, as reflected in the measuredproperties of flexural strength and fracture toughness. Hence, there isstill a need for new monomers and new monomer combinations which, whenpolymerized, impart high fracture toughness and flexural strength in theresulting composite. It is also highly desirable to have low shrinkagestress on polymerization.

One of the more common commercially used monomers is Bis-GMA. However,it is highly viscous at room temperature and difficult to work with. Itis therefore diluted with a second, lower viscosity polymerizablecomponent (“fluidizer”), a methacrylate monomer, such as TEGDMA,tetraethylene glycol dimethacrylate, or docecanediol dimethacrylate.However, while providing low viscosity, lower viscosity components(generally low molecular weight monomers) can contribute to increasedshrinkage. Increasingly, Bis-GMA and TEGDMA have been combined with UDMAand EBPDMA, but shrinkage remains high enough that improvement isdesirable.

A more efficient and effective fluidizing monomer that would allowdental composites to be formulated with higher proportions of thehigh-viscosity monomer while not compromising the mechanical propertiesor polymerization shrinkage of the system is a desirable invention. Aneffective fluidizing monomer could also allow the composite to beformulated at a higher filler level, further lowering shrinkage.

(Meth)acrylated adducts of caprolactone and tricyclodecanemethylol havebeen described as resinous coating materials for optical fibers in U.S.Pat. No. 4,843,111, but not for dental composite applications.

An adduct prepared by reaction of cyclohexanedimethanolmono(meth)acrylates with lactones has been described in JP 2000016967for coating systems, but not for dental composite applications.

Adducts prepared by reaction of cyclohexanedimethanol with caprolactoneand subsequently (meth)acrylated have been described in JP2000169431 forinks, but not for dental composite applications.

Adducts of 1,4-cyclohexanedimethanol and caprolactone, not(meth)acrylated, have been described in U.S. Pat. No. 5,159,047 forcoating systems, but not for dental composite applications.

A copolymer of adipic acid (erroneously translated from the Japanese as“acrylic acid” in Chemical Abstracts 136:233450), ε-caprolactone, and2-methyl-1,1-cyclohexanedimethanol has been described in JP 2002069163as a precursor to spandex filaments, but not for dental compositeapplications.

There thus remains a need for efficient and effective fluidizingmonomers for dental composite materials that combine reduced shrinkagewith sufficiently low viscosity, high polymerization rate, andacceptable mechanical properties.

SUMMARY OF THE INVENTION

In its first aspect, the present invention is an uncured dentalcomposite material that comprises

(i) a composition comprising at least one compound having the Formula I:E¹-R¹ _(n)—O—R²-Q-R³—O—R⁴ _(m)-E²  Iwherein:

-   Q is selected from the group consisting of:

(a) a carbocyclic ring containing 5 or 6 carbon atoms with up to 3 C₁₋₃alkyl substituents on the ring;

(b) S—R⁵-T wherein S and T are each independently carbocyclic ringscontaining 5 or 6 carbon atoms with up to 3 C₁₋₃ alkyl substituents onthe ring, and R⁵ is a covalent bond or an alkylene group containing 1,2, 3 or 4 carbon atoms; and

(c) a carbocyclic fused ring system containing two fused ringscontaining a total of 8 to 10 carbon atoms with up to 4 C₁₋₃ alkylsubstituents on the fused ring system;

-   R² and R³ are each independently selected from the group consisting    of a covalent bond and an alkylene group containing 1, 2, 3, or 4    carbon atoms;-   R¹ is a repeat unit of the formula

-   R⁴ is a repeat unit of the formula

-   E¹ and E² are each independently

wherein R⁶ is H (acrylyl) or CH₃ (methacrylyl); and

-   n and m are each independently an integer greater than 0;    -   provided that for each of the n groups of the formula

-   a is independently an integer from 3 to 6; and-   provided that for each of the m groups of the formula

-   a′ is independently an integer from 3 to 6;-   provided that neither R² nor R³ is a covalent bond bonded directly    to an aromatic ring;-   and provided that the degree of polymerization (dp=n+m) of the    compound is between 2 and 30;

(ii) optionally at least one additional polymerizable (meth)acrylicester;

(iii) at least one polymerization initiator compound; and

(iv) at least one filler.

In its second aspect, the present invention is an uncured dentalcomposite material incorporating at least one compound of Formula I, atleast one polymerization initiator compound, at least one filler, and atleast one compound of the Formula II:

wherein:

each R⁷ is independently hydrogen or methyl;

each R⁸ is an alkylene having 2 to 14 carbon atoms, or an alkenylenehaving 2 to 8 carbon atoms, or a divalent alicyclic hydrocarbon having 5to 14 carbon atoms, or a phenylene, which is optionally substituted withhalogen or an alkyl group having 1 to 5 carbon atoms;

each R⁹ is independently selected from hydrogen, acetyl, methyl, ethyl,C₃₋₆ linear or branched alkyl, or benzyl;

R¹⁰ is independently selected from hydrogen, methyl, ethyl, C₃₋₆ linearor branched alkyl, phenyl, or benzyl; and

each A is a repeating unit of the formula:

wherein:

each R¹¹ is independently an alkylene having 2 or 3 carbon atoms,

each R¹² is independently an alkylene having 2 to 7 carbon atoms,

each R¹³ is independently an alkylene having 2 to 5 carbon atoms,

p is an integer of 1 to 10,

and q is an integer of 1 to 10.

In its third aspect, the present invention is an uncured dentalcomposite material incorporating at least one compound of Formula I, atleast one polymerization initiator compound, at least one filler, and atleast one compound of the Formula V:

wherein R⁷, A, R⁸, R⁹, are as defined in relation to the compound ofFormula II, and each R¹⁴ is independently selected from the groupconsisting of hydrogen, methyl, ethyl, C₃₋₆ linear or branched alkyl,phenyl, benzyl, and the two R¹⁴ groups may be taken together to form asubstituted or unsubstituted cyclic aliphatic ring having 5 or 6 carbonsin the ring, including the carbon to which both R¹⁴ groups are attached.

DETAILED DESCRIPTION OF THE INVENTION

In the context of this application, a number of terms are utilized.

The term “dental composite material” as used herein denotes acomposition that can be used to remedy natural or induced imperfectionsin, or relating to, teeth. Examples of such materials are fillingmaterials, reconstructive materials, restorative materials, crown andbridge materials, inlays, onlays, laminate veneers, dental adhesives,teeth, facings, pit and fissure sealants, cements, denture base anddenture reline materials, orthodontic splint materials, and adhesivesfor orthodontic appliances. The term “uncured dental composite material”specifically refers to such material before it is subjected to a curingprocess.

As used herein, the term “alkyl” means a univalent group derived from analkane by removing a hydrogen atom from any carbon atom: —C_(n)H_(2n+1)where n≧1.

As used herein, the term “hydrocarbyl”, when used in relation to aradical, denotes a univalent radical containing only carbon andhydrogen.

As used herein, the term “alkylene” means the divalent radical derivedfrom an alkane by removing a hydrogen atom from each of two differentcarbon atoms: —C_(n)H_(2n)— where n≧1.

As used herein, the term “alkenylene” means a straight or branched chainalkenediyl containing one olefinic bond in the chain, e.g. —CH═CH—(ethenylene), —CH₂CH═CH— (propenylene), etc.

As used herein, the term “carbocyclic” means having or relating to orcharacterized by a ring composed of carbon atoms.

As used herein, “an alicyclic group” means a non-aromatic hydrocarbongroup containing a cyclic structure therein.

As used herein, the term “benzyl” refers to the C₆H₅CH₂— radical.

As used herein, the term “phenyl” refers to the C₆H₅— radical.

As used herein, the term “phenylene” refers to the divalent radical,—C₆H₄—:

As used herein, the term “cyclohexylene” refers to the divalent radical,—C₆H₁₀—:

As used herein, the term “carboxy methacrylate” means a compoundcontaining a carboxylic acid and a methacrylate group.

As used herein, the terms “(meth)acrylic” and “(meth)acrylate” refer toboth methacrylic and acrylic and to methacylate and acrylate,respectively.

As used herein, the terms “acrylyl” and “methacrylyl” refer to theunivalent radicals

respectively.

As used herein, the term “polymerizable (meth)acrylic ester component”means one or more materials that bear (meth)acrylate groups, such thatthe materials are capable of undergoing free radical polymerization.

As used herein, the term “diol” means an organic compound having twohydroxyl (—OH) groups per molecule.

As used herein, the term “caprolactone” means ε-caprolactone, CASRegistry #502-44-3:

As used herein, the term “1,4,-cyclohexanedimethanol” refers to thematerial designated by CAS Registry #105-08-8:

Where a range of numerical values is recited herein, unless otherwisestated, the range is intended to include the endpoints thereof, and allintegers and fractions (provided the context allows) within the range.

The degree of polymerization, abbreviated dp, of a compound of Formula Iis defined as the sum of the number of repeat units R¹ and R⁴. Theaverage dp for a given sample of a heterogeneous composition comprisingdifferent molecules of Formula I is defined by the average of the dp'sfor each molecule of Formula I in the sample.

(Meth)Acrylated Polyester Diols

The present invention provides a dental composite material comprising a(meth)acrylated polyester diol composition containing at least onecompound of the Formula I, as shown below.E¹-R¹ _(n)—O—R²-Q-R³—O—R⁴ _(m)-E²  Iwherein:

-   Q is selected from the group consisting of:

(a) a carbocyclic ring containing 5 or 6 carbon atoms with up to 3 C₁₋₃alkyl substituents on the ring;

(b) S—R⁵-T wherein S and T are each independently carbocyclic ringscontaining 5 or 6 carbon atoms with up to 3 C₁₋₃ alkyl substituents onthe ring, and R⁵ is a covalent bond or an alkylene group containing 1,2, 3 or 4 carbon atoms; and

(c) a carbocyclic fused ring system containing two fused ringscontaining a total of 8 to 10 carbon atoms with up to 4 C₁₋₃ alkylsubstituents on the fused ring system;

-   R² and R³ are each independently selected from the group consisting    of a covalent bond and an alkylene group containing 1, 2, 3, or 4    carbon atoms;-   R¹ is a repeat unit of the formula

-   R⁴ is a repeat unit of the formula

-   E¹ and E² are each independently

wherein R⁶ is H (acrylyl) or CH₃ (methacrylyl); and

-   n and m are each independently an integer greater than 0;-   provided that for each of the n groups of the formula

-   a is independently an integer from 3 to 6; and-   provided that for each of the m groups of the formula

-   a′ is independently an integer from 3 to 6;-   provided that neither R² nor R³ is a covalent bond bonded directly    to an aromatic ring;-   and provided that the degree of polymerization (dp) of the compound    is between 2 and 30.

Examples of Q wherein Q is a carbocyclic ring containing 5 or 6 carbonatoms with up to 3 C₁₋₃ alkyl substituents on the ring include, but arenot limited to:

Examples of Q wherein Q is S—R⁵-T wherein S and T are each independentlycarbocyclic rings containing 5 or 6 carbon atoms with up to 3 C₁₋₃ alkylsubstituents on the ring, and R⁵ is a covalent bond or an alkylene groupcontaining 1, 2, 3 or 4 carbon atoms include, but are not limited to:

Examples of Q wherein Q is a carbocyclic fused ring system containingtwo fused rings containing a total of 8 to 10 carbon atoms with up to 4C₁₋₃ alkyl substituents on the fused ring system include, but are notlimited to:

It is preferred that R² and R³ are identical and that each is a covalentbond or methylene (—CH₂—).

In a preferred embodiment of the invention Q is a carbocyclic ring, morepreferably it is cyclohexylene, most preferably 1,4-cyclohexylene.

When Q is S—R⁵-T it is preferred that R⁵ is 2,2-propylene or methylene.It is also preferred that S and T are each cyclohexylene, and morepreferred that S and T are 1,4-cyclohexylene.

In a preferred embodiment of this invention, herein referred to as“DM-CL-CHDM,”, Q is 1,4-cyclohexylene, R²═R³═CH₂, a=a′=5, R⁶ is CH₃, andthe dp is 2 to 6.

The present invention provides dental composite materials comprising(meth)acrylated polyester diol compounds of Formula I. These(meth)acrylated polyester diol compounds are produced by a process of(1) preparing a polyester diol, and (2) converting greater than 90%,preferably all, of the terminal hydroxyl groups of the polyester diol to(meth)acrylate groups.

The polyester diol can be produced by heating a mixture that includes

-   (1) at least one lactone

-   -   where r=a or a′ as defined above;

-   (2) a diol, HO—R²-Q-R³—OH, where R², Q, and R³ are defined as above;    and

-   (3) optionally a polyester polymerization catalyst (see below); and

-   (4) optionally a solvent.

Some solvents suitable for this reaction are toluene, benzene, p-xylene,m-xylene, o-xylene, and mixtures thereof. In a preferred embodiment ofthis invention the reaction is run without a solvent.

Typical polyester polymerization catalysts that are useful in thisreaction include, but are not limited to, dibutyl tin dilaurate, dibutyltin diacetate, Sn(2-ethylhexanoate)₂, Sn(n-octanoate)₂;p-toluenesulfonic acid; and methanesulfonic acid. Tin(II) catalysts arepreferred.

The polyester diol is then combined and optionally heated with one ormore end capping agents selected from (meth)acrylic acid, (meth)acryloylchloride, and (meth)acrylic anhydride. It is preferred that at least 90%of the diol ends be capped with a (meth)acrylate cap. The degree ofcapping with radically polymerizable end groups can be determined by acombination of ¹H NMR, ¹³C NMR and two-dimensional NMR spectroscopy.

Some solvents for suitable for this capping reaction are tetrahydrofuran(“THF”), diethyl ether, pyridine, N,N-dimethylacetamide,N,N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, CH₂Cl₂,CHCl₃, chlorobenzene, o-dichlorobenzene, benzene, toluene, xylene, andmixtures thereof. Preferably the reaction is run without a solvent.

When a solvent is not used, the reaction product is typically washedwith an aqueous basic solution, such as saturated Na₂CO₃ (aq), to removeacidic impurities. It is then washed with water and finally withsaturated NaCl solution to remove the bulk of the water. It isoptionally dried with a drying agent, such as Na₂SO₄, to remove finaltraces of water.

When a solvent is used, the reaction product is typically isolated byeither of two methods. The first method involves an aqueous workup. Theorganic phase is typically washed with an aqueous basic solution, suchas saturated Na₂CO₃ (aq), to remove acidic impurities. It may optionallybe washed with dilute aqueous acidic solution (e.g., 10% HCl) to removebasic impurities such as pyridine. Then it is washed with saturated NaClsolution to remove the bulk of the water. It is optionally dried with adrying agent, such as anhydrous Na₂SO₄, to remove final traces of water.Then the organic solvent is removed, optionally under vacuum, to obtainthe final product. A second method for isolating the product is toperform a high vacuum distillation directly on the reaction mixture.This is typically done at 0.5 torr (66 Pa) to distill off methacrylicacid and unreacted methacrylic anhydride. The second method typically isnot used when methacryloyl chloride is used as the capping agent.

It will be recognized by one skilled in the art that while the dp ofindividual molecules of Formula I will vary, the average degree ofpolymerization, dp, for a given sample of a heterogeneous compositioncomprising different molecules of Formula I will be determined by theoriginal molar ratio of the lactone to the diol that was used to preparethe sample, assuming the reaction was carried to completion.

Expressed in greater detail, a preferred (meth)acrylated polyester diolcan be made by a process comprising the steps of:

-   -   (a) combining caprolactone, 1,4-cyclohexanedimethanol in the        molar ratio of 2:1 to 6:1, dibutyl tin dilaurate, and xylene;    -   (b) slowly heating the mixture to 140 C, and holding for four        hours;    -   (c) cooling the mixture to 80° C. and filtering the product;    -   (d) combining the product from step (c) with methacrylic        anhydride and sodium acetate;    -   (e) heating the mixture from step (d) to 80° C. under air for 6        hours;    -   (f) adding the product from step (e) to an aqueous solution of        sodium carbonate with stirring for 1 hr;    -   (g) combining the mixture from step (f) with ethyl ether and        then stirring the resulting mixture for 12 hr;    -   (h) separating the mixture from step (g) into its organic and        aqueous phases;    -   (i) washing the organic phase from step (h) first with water and        then with a concentrated, aqueous sodium chloride solution;    -   (j) drying the solution from step (i) over anhydrous sodium        sulfate;    -   (k) combining the dried solution from step (j) with MEHQ    -   (l) concentrating the solution from step (k) in vacuo to give        the desired product.

The (meth)acrylated polyester diols of the present invention are alsoexpected to be useful in applications other than dental composites,particularly in coating systems, for example, for coating metals, forindustrial finishes, wood finishes, and for coating hard plastics.

Dental Composite Materials

The present invention further provides an uncured dental compositematerial comprising:

-   -   (a) at least one compound of Formula I    -   (b) optionally at least one other polymerizable (meth)acrylic        ester;    -   (c) at least one polymerization initiator compound; and    -   (d) at least one filler.

Other Polymerizable (Meth)Acrylic Ester Component

Examples of suitable materials for the polymerizable (meth)acrylic estercomponent include but are not limited to2,2′-bis[4-(2-hydroxy-3-methacryloyloxypropyl)phenyl]propane(“Bis-GMA”); ethoxylated Bisphenol A dimethacrylate (“EBPDMA”);1,6-bis-[2-methacryloyloxyethoxycarbonylamino]-2,4,4-trimethylhexane(“UDMA”); 1,1,1-tri[4-2-methyl-2-methacryloxyethoxy)-phenyl]ethane(“THPE PO MA”); and butanedioic acid,ethylidynetris[4,1phenyleneoxy(2-hydroxy-3,1-propanediyltris[2-[[(2-methyl-1-oxo-2-propenyl)oxy]ethyl]ester. (“THPE GE Su-HEMA”).

A preferred additional polymerizable (meth)acrylic ester componentaccording to the present invention comprises a compound of Formula II asfollows:

wherein:

each R⁷ is independently hydrogen or methyl;

each R⁸ is an alkylene having 2 to 14 carbon atoms, or an alkenylenehaving 2 to 8 carbon atoms, or a divalent alicyclic hydrocarbon having 5to 14 carbon atoms, or a phenylene, which is optionally substituted withhalogen or an alkyl group having 1 to 5 carbon atoms;

each R⁹ is independently selected from hydrogen, acetyl, methyl, ethyl,C₃₋₆ linear or branched alkyl, or benzyl;

R¹⁰ is independently selected from hydrogen, methyl, ethyl, C₃₋₆ linearor branched alkyl, phenyl, or benzyl; and

each A is a repeating unit of the formula:

wherein:

each R¹¹ is independently an alkylene having 2 or 3 carbon atoms,

each R¹² is independently an alkylene having 2 to 7 carbon atoms,

each R¹³ is independently an alkylene having 2 to 5 carbon atoms,

p is an integer of 1 to 10,

and q is an integer of 1 to 10.

A particularly preferred compound of Formula II is butanedioic acid,ethylidynetris[4,1phenyleneoxy(2-hydroxy-3,1-propanediyltris[2-[[(2-methyl-1-oxo-2-propenyl)oxy]ethyl]ester (“THPE GE Su-HEMA”):

One method of preparing the compound of Formula II is the following:

Triepoxides of Formula III are commercially available. For example,compound II where R¹⁰=methyl (i.e., 1,1,1-tris(p-hydroxyphenylethane)triglycidyl ether), is available from E. I. du Pont de Nemours & Co.,Inc. (Wilmington, Del.) under the trade name THPE-GE. Other compounds ofFormula III (where R¹⁰ is defined as above) can be prepared by thescheme below.

A compound of Formula III is treated with at least three moles of thecarboxy methacrylate compound of Formula IV. The carboxylic acid ofFormula IV opens the epoxide rings in Formula III to give the desiredproduct. The reaction gives the hydroxy compound (R⁹═H). The hydroxycompound can be further alkylated or acylated by any means known in theart. For example, it can be treated with acetic anhydride to give theacetylated product (R⁹═—C(O)CH₃).

Suitable carboxy methacrylate compounds can be prepared by treatment of,for example, hydroxyethyl(meth)acrylate or hydroxypropyl (meth)acrylatewith a cyclic anhydride to give the corresponding carboxy methacrylatecompound. Preferred anhydrides include succinic anyhydride, maleicanhydride, and phthalic anhydride. Other suitable anhydrides include,those containing an anhydride function as part of a five or six memberring.

Some examples of syntheses and structures of carboxy methacrylates (IVA,IVB, IVC) are shown below.

Other suitable carboxy methacrylates are described in U.S. Pat. No.4,883,899, Col 2, line 37 to Col 3, line 17. There, hydroxyethylmethacrylate is used as an initiator for the ring opening polymerizationof caprolactone. The resulting hydroxy methacrylates are commerciallyavailable from Daicel Chemical Industries, Ltd. (Tokyo, Japan) under thetrade name Placcel. For example, Placcel FM 3 is the addition product ofhydroxyethyl methacrylate with three moles of caprolactone. Theseproducts can be reacted with cyclic anhydrides to give carboxyfunctional methacrylates useful in the present invention.

Catalysts for the reaction may include any known in the art for thereaction of carboxylic acids with epoxides. They may includenitrogen-containing compounds such as triethylamine, imidazole, 2-methylimidazole, N,N-dimethyl benzyl amine, pyridine, and the like. They mayinclude Lewis acids such as zinc acetate or zinc stearate.

These compounds can be purified by any method indicated to one skilledin the art. Typical purification procedures might include extraction,distillation, crystallization and preparative chromatography.

In a preferred uncured dental composite, the compounds of Formula I andFormula II are used in a weight ratio of ranging from about 1:99 to25:75. At this weight ratio, the viscosity of the uncured dentalcomposite is low enough to allow fillers to be added and adequatelymixed. The resulting material, when cured, shows relatively lowshrinkage with good mechanical properties.

Another compound that may be used in addition to, or in place of, acompound of Formula II is a compound of Formula V.

wherein R⁷, A, R⁸, R⁹, are as defined in relation to the compound ofFormula II, and each R¹⁴ is independently selected from the groupconsisting of hydrogen, methyl, ethyl, C₃₋₆ linear or branched alkyl,phenyl, benzyl, and the two R¹⁴ groups may be taken together to form asubstituted or unsubstituted cyclic aliphatic ring having 5 or 6 carbonsin the ring, including the carbon to which both R¹⁴ groups are attached.

A preferred compound of Formula V is shown below.

Such compounds may be synthesized as shown below.

Some of the compounds of Formula V have been described in, for example,U.S. Pat. No. 3,367,992 Col. 6, line 27 to Col. 7, line 21, although notin relation to use in dental composites.

The polymerizable (meth)acrylic ester component may include additionalpolymerizable (meth)acrylic ester compounds. These additionalpolymerizable (meth)acrylic ester compounds may include bothmonofunctional compounds and polyfunctional compounds, where“monofunctional” denotes a compound having one (meth)acrylic group and“polyfunctional” denotes a compound having more than one (meth)acrylicester group.

Other examples of polyfunctional (meth)acrylic ester compounds include,without limitation, Bis-GMA, EBPDMA, UDMA, and other urethanedi(meth)acrylates.

Polymerization Initiator Compounds

Suitable polymerization initiator compounds include peroxy-typeinitiators such as benzoyl peroxide, dicumyl peroxide, lauryl peroxide,tributyl hydroperoxide, and other materials familiar to those skilled inthe art. Azo-type initiators such as 2,2′-azobis(isobutyronitrile),2,2′-azobis(2,4-dimethyl valeronitrile), 2,2′-azobis(2-methyl butanenitrile), and 4,4′-azobis(4-cyanovaleric acid) may also be used.

A preferred initiator system is the photosensitizer camphorquinone, usedin conjunction with a tertiary amine like ethyl dimethylaminobenzoate ordimethylaminoethyl methacrylate.

The polymerization initiator (optionally with a photosensitizer) can beused in the range of about 0.1 weight percent to about 5 weight percent,preferably about 0.2 weight percent to about 3 weight percent, and morepreferably about 0.2 weight percent to about 2 weight percent. Thepercentages are based on the total weight of the uncured dentalcomposite, exclusive of filler.

Fillers

One class of fillers that may be used in the uncured dental compositesof the present invention is inorganic fillers. Among the preferredinorganic fillers are barium aluminum silicate, barium aluminumborosilicate, ytterbium trifluoride, glass beads, silica, quartz,borosilicates, alumina, and alumina silicates, Mixtures of inorganicfillers may also be employed. The mean particle size of the inorganicfillers is preferably between about 0.5 and 15 μm.

Another class of fillers that may be used in the uncured dentalcomposites of the present invention is organic fillers. Suitable organicfillers include prepolymerized fillers (“prepolymerized” in the sensethat organic monomers have been polymerized to produce an organic resin,which, optionally, can be ground, prior to their inclusion in theuncured dental composites of this invention). Such prepolymerizedfillers may be included in the uncured dental composites of theinvention alone or in combination with an inorganic filler. Theseprepolymerized fillers can also optionally contain inorganic fillerssuch as those described above.

The total amount of filler in the uncured dental composites of thepresent invention can range from about 20 weight percent to about 90weight percent, preferably from about 40 weight percent to about 90weight percent, and more preferably from about 50 weight percent toabout 85 weight percent. The percentages are based on the total weightof the uncured dental composite.

Additional Optional Ingredients

In addition to the components described above, the composite materialmay contain additional, optional ingredients. These may compriseactivators, pigments, radiopaquing agents, stabilizers, antioxidants,and other materials.

The uncured dental composite material of the present invention can beprepared using any mixing means known in the art. Such methods include,but are not limited to, roll mills, vibratory mixers, sigma mixers,planetary mixers, SpeedMixers™ (from Flack Tek, Inc., Landrum, S.C.),extruders, Buss Kneaders (Coperion Holding GmbH, Stuttgart, Germany),and Brabender Plasticorders® (Intellitorque, Brabender, Hackensack, N.J.

The dental composite materials of the present invention can be used tofill cavities in teeth. Other treatments may include preventative,restorative, or cosmetic procedures in teeth. Typically, withoutlimiting the method to a specific order of steps, the dental compositematerials are placed on dental tissue, either natural or synthetic,cured, and shaped as necessary to conform to the target dental tissue.Dental tissue includes, but is not limited to, enamel, dentin, cementum,pulp, bone, and gingiva.

The dental composite materials may also be useful as dental adhesives,primers, bonding agents, pit and fissure sealants, cements, denture baseand denture reline materials, orthodontic splint materials, andadhesives for orthodontic appliances. The materials also may be usefulfor making bridges, crowns, inlays, onlays, laminate veneers, andfacings. The materials of the invention also may be useful forprosthetic replacement or repair of various hard body structures such asbone and also may be useful for reconstructive purposes during surgery,especially oral surgery.

EXAMPLES

The present invention is further defined in the following Examples. Itshould be understood that these Examples, while indicating preferredembodiments of the invention, are given by way of illustration only.From the above discussion and these Examples, one skilled in the art canascertain the essential characteristics of this invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various uses andconditions.

Abbreviations

The meaning of abbreviations is as follows: “hr” means hour(s), “min”means minute(s), “mL” means milliliter(s), “m” means meter, “cm” meanscentimeter(s), “mm” means millimeter(s), “μm” means micrometer(s), “nm”means nanometer(s), “g” means gram(s), “mol” means mole(s), “mmol” meansmillimoles, “N” means Newton(s), “rpm” means revolutions per minute, “wt%” means weight percent(age), “mW” means milliwatt(s), “Mw” means weightaverage molecular weight, “MPa” means megaPascal(s), “MHz” meansmegaHertz, “std dev” means standard deviation, “avg dev” means averagedeviation, “d50” means 50% of particles have a diameter below a givensize, “EtOAc” means ethyl acetate, “MEHQ” means 4-methoxyphenol, “PTFE”means polytetrafluoroethylene, “THF” means tetrahydrofuran, “NMR” meansnuclear magnetic resonance (spectroscopy), “IR” means infrared(spectroscopy), “ATR” means attenuated total reflectance, “DSC” meansdifferential scanning calorimetry, “GPC” means gel permeationchromatography, “THPE GE” means 1,1,1-tris(p-hydroxyphenyl) ethanetriglycidyl ether, “Bis-GMA” means bisphenol-A-glycidyl methacrylate,“TEGDMA” means triethylene glycol dimethacrylate, and “EDB” means ethyl4-dimethylaminobenzoate.

Materials

1,1,1-tris(p-hydroxyphenyl) ethane triglycidyl ether (“THPE GE”) wasobtained from E. I. du Pont de Nemours & Co., Inc. (Wilmington, Del.).Caprolactone was obtained from Dow Chemical Company (Midland, Mich.).Mono-2-(methacryloyloxy)ethyl succinate, methacrylic anhydride (Aldrichcatalog #276685, stabilized with 2000 ppm of 2,4-dimethyl-6-tert-butylphenol), and MEHQ were obtained from Aldrich Chemical Company(Milwaukee, Wis.). 1,4-cyclohexanedimethanol (CAS #105-08-8, Eastmanproduct code # CHDM-D) was obtained from Eastman Chemical Company(Kingsport, Tenn.), Bisphenol-A-glycidyl methacrylate adduct (“Bis-GMA”)was obtained from EssTech (Essington, Pa.), product code X 950-0000.Triethylene glycol dimethacrylate (“TEGDMA”) was obtained from EssTech(Essington, Pa.), product code product code X 943-7424, inhibited withhydroquinone (50-70 ppm). Photosensitizers were obtained from AldrichChemical Company (Milwaukee, Wis.): camphorquinone (97%, catalogue#12,489-3) and ethyl 4-dimethylaminobenzoate (99+%, catalogue #E2,490-5). Aerosil® OX-50 fumed silica was obtained from Degussa(Dusseldorf, Germany). Schott 8235 UF1.5 glass powder was obtained fromSchott AG (Mainz, Germany); it had a mean diameter, d50, of 1.5 μm andwas treated with C₁₀H₂₀O₅Si to a level of 2.3 wt % silane.Sample Preparation

Uncured compositions intended for testing were packed into a stainlesssteel 2 mm thick mold with at least one 2 mm×25 mm opening to enable twosides of the uncured composition to be exposed. The packed mold wassandwiched on either side with a polyester film, followed a glass plate.Bars of the uncured compositions were cured for the length of time perside and light intensities specified.

Analytical Methods

Molecular weight was determined by gel permeation chromatography (GPC)in THF using polystyrene standards.

The degree of monomer polymerization (“conversion”) was measured byFourier Transform Infrared (FTIR) spectroscopy, using the totalattenuated reflectance (ATR) method. The absorbances of the IR peaks at1610 cm⁻¹ (corresponding to aromatic C═C stretch) and 1640 cm⁻¹(corresponding to methacrylate C═C stretch) were measured before andafter irradiation. The peak absorbances were all normalized usingappropriate baselines, and a % C═C value and a DC value were calculatedaccording to the equations below, using normalized absorbance values:% C═C=[(A ₁₆₄₀ /A ₁₆₁₀)_(after)/(A ₁₆₄₀ /A ₁₆₁₀)_(before)]×100DC(degreeof conversion)=100−% C═CThe DC is referred to as the “C-Peak” degree of conversion.

The so-called “E-Peak” degree of conversion was also measured asdescribed in Dental Materials (1990), 6(4), 241-249. This alternativemethod uses the ratio of the 1640 cm⁻¹ and the 1580 cm⁻¹ peaks, ratherthan the 1640 cm⁻¹ and 1610 cm⁻¹ peaks. The baseline of the 1640 cm⁻¹peak is defined by drawing a baseline from the value at 1660 cm⁻¹ to thevalue at about 1590 cm⁻¹.

Fracture toughness (K_(IC)), flexural strength (ISO 4049), and densitywere determined on (2 mm×2 mm×25 mm) bars that were molded using thestainless steel mold described above. The molded bars were cured in themold by irradiating each exposed side for 1 minute using either

a) an array of three Spectrum® 800 dental lamps (DENTSPLY International,York, Pa.), each bearing an 8-mm light tip, at 550 mW/cm², or

b) a Fusion UV Systems Inc.® (Gaithersburg, Md.) curing unit equippedwith a Q-bulb (designed for emitting light at a wavelength suitable forcamphorquinone excitation).

The metal mold was covered on both sides with a 3-mil (76-micron)polyester film to exclude oxygen.

Five bars were used for each of the fracture toughness and flexuralstrength tests. The bars were stored in glass vials until use andconditioned in water for 24 hr at 37° C., just prior to the tests.

The fracture toughness test was based on both the ASTM polymers standard(ASTM D5045) and the ASTM ceramics standard (ASTM C1421, precracked beammethod). Testing was conducted at a test speed of 0.5 mm/min at roomtemperature and ambient humidity using a three-point bend fixture (spanto depth ratio of 10). The specimens were molded using the flex bar moldspecified in ISO 4049. The specimens were precracked halfway throughtheir depth. Two modifications to the test procedures were made. Thefirst was the use of smaller test specimens than those recommended inthe ASTM C1421 standard (2 mm×2 mm×25 mm instead of the recommendedminimum dimensions of 3 mm×4 mm×20 mm). The second was the use of aslitting circular knife to machine the precracks. The knife was 0.31 mmin thickness with a 90° single bevel. The modified test proceduresproduced precracks that were equivalent to precracks produced using thetechniques recommended in ASTM D5045.

The percent shrinkage (% S) was determined by measuring the densities ofuncured dental composites and of cured dental composites. The volumeswere measured with an AccuPyc 1330 Pycnometer for 1-cm³ Samples(Micromeritics Instrument Corporation, Norcross, Ga.), using argon. Thedensity of the uncured dental composites was determined by measuring thevolume of a known weight of composite (measured by an analytical balancewith a resolution of ±0.0001 g). Briefly, the pycnometer was set up for5 purges and 3 volume measurements per sample. The volume of a glass cup(about 0.36 cubic centimeters) and, then, the cup containing uncuredcomposite (about 0.3 to 1 g) were measured sequentially. The volume ofthe uncured dental composite was calculated by subtracting the volume ofthe glass cup from the total volume of the cup with the uncured dentalcomposite. The density of uncured composite ρ_(uncured) is defined asgrams of uncured composite divided by volume of uncured composite incubic centimeters. The uncured paste was then pressed thin between twosheets of Mylar® polyester film and cured in a Triad® 2000™ VisibleLight Curing Unit (DENTSPLY International) for two minutes on each side.The cured film was peeled from the Mylar® and ground to a coarseparticulate with a mortar and pestle. The density of the cured dentalcomposite was calculated in a manner similar to that of uncuredcomposite as described above. The density of cured composite ρ_(cured)is defined as grams of cured composite divided by volume of curedcomposite in cubic centimeters.

The percent shrinkage (% S) was calculated from the formula,[(ρ_(cured)−ρ_(uncured))/(ρ_(cured))]×100=% S.

Example 1 Preparation and Purification of THPE GE Su HEMA

A 1 L three neck flask equipped with a mechanical stirrer, condenser,thermocouple, and addition funnel was charged with THPE GE (112.5 g),mono-2-(methacryloyloxy)ethyl succinate (218.3 g), triethylamine (1.2g), and Prostab® 5415 (0.2 g,). The mixture was heated to 80° C. for 7.5hr to obtain a pale yellow mixture. The mixture was dissolved in 1250 mLof ethyl acetate, extracted with 500 mL of water followed by 500 mL ofsaturated sodium bicarbonate solution. The solution was dried withanhydrous sodium sulphate, then added to 1 liter of silica gel (Mercksilica gel 60), and the solvent was removed. The silica gel containingthe compound was then added to a column with 2500 g of silica gel andwas eluted with a mixture of hexanes and ethyl acetate to isolate apurified fraction of the desired compound, THPE GE Su HEMA. ¹H NMR (500MHz, CDCl₃) δ 1.93 (s, 9H), 2.08 (s, 3H), 2.61-2.7 (m, 12H), 3.84-4.2(m, 15H), 4.3-4.4 (m, 12H), 5.6 (m, 3H), 6.1 (m, 3H), 6.75 (m, 6 H),6.98 (m, 6H).

Example 2 Preparation of dimethacrylatedε-caprolactone-1,4-cyclohexane-dimethanol adduct (“DM-CL-CHDM”)

An adduct was made by heating three moles of caprolactone with one moleof 1,4-cyclohexanedimethanol at 140° C. for four hours with 0.01 wt.percent of dibutyltin dilaurate and 0.1 wt. percent of xylene. Thematerial was then cooled to 80° C. and purified by filtration through asparkler filter.

A solution of the ε-caprolactone-1,4-cyclohexanedimethanol adduct(average Mw=487; 194 g, 398 mmol, 797 mmol reactive OH), methacrylicanhydride containing 2000 ppm of Topanol A (140 g, 908 mmol) and sodiumacetate (1.40 g, 17.1 mmol) was heated to 75-80° C. for 6 hr under aconstant flow of dry air. After cooling to room temperature, theresulting product mixture was stirred with 5% aqueous sodium carbonate(500 mL) for 1 hr. The mixture was then treated with ethyl ether (300mL) and stirred gently overnight. The mixture was allowed to separateinto organic and aqueous fractions and the aqueous fraction wasdiscarded. The organic (ether) fraction was washed first with 5% aqueoussodium carbonate (2×300 mL), then with water (6×200 mL) and finally withbrine (concentrated, aqueous sodium chloride solution) (100 mL). Theether solution was dried over anhydrous sodium carbonate and thentreated with MEHQ (0.050 g). The resulting solution was concentrated invacuo with mild heating to give a clear oil. The oil, maintained at roomtemperature, was further concentrated by first applying a reduced vacuum(ca. 20 torr, with filtered air-bleed) for 4 hr, followed by high vacuumfor 3 hr, ultimately furnishing 210 gm of the product.

IR spectroscopy of the neat product showed an absence of OH stretchingbetween 3450 and 3550 cm⁻¹. Additionally, a strong ester peak centerednear 1732 cm⁻¹ and a peak at 1637 cm⁻¹ representing the methacrylatedouble bond were noted in the IR spectrum. ¹H NMR spectroscopy (inCDCl₃) confirmed the presence of terminal methacrylate groups in theproduct, with vinylic proton resonances near 5.5 (1H) and 6.1 ppm (1H).

Examples 3, 4, and 5 Dental Composite Materials Made With THPE-GE SuHEMA and 2 to 10 wt % DM-CL-CHDM

Dental composite materials were made using a first monomer component,the purified THPE GE Su HEMA from Example 1, and a second monomercomponent, the dimethacrylated ε-caprolactone-1,4-cyclohexanedimethanoladduct from Example 2. Photoinitiators used were camphorquinone and EDB.Fillers used were Schott 8235 glass and Degussa Aerosil® OX-50.

The monomer components, photoinitiators, and fillers were combined, inthe amounts noted in Table 1, in the “max 40” size cup of a Flack TekSpeedMixer® under yellow light to avoid premature polymerization. Thecontents were mixed for two 30-second intervals at 3500 rpm. The mixturewas wrapped in foil to exclude light and transferred to a Sigma mixer(“B&P Model 2 cubic inch Horizontal Batch Mixer”, B&P Process Equipmentand Systems LLC, 1000 Hess Ave., Saginaw, Mich., USA) preheated to 45°C. The sample was mixed under yellow light for 15 minutes at 10 rpm atatmospheric pressure, 15 minutes at 20 rpm at atmospheric pressure, and30 minutes at 15 rpm under a vacuum of 210 torr. Any buildup of pasteabove the mixer blades was pushed material down into the main part ofthe mixture, with a spatula between each of the steps. The resultingpaste was stored in a foil-wrapped container to exclude light andrefrigerated until use, to prevent premature curing.

The paste was formed into bars, cured, and tested as described above.Results are presented in Table 1.

TABLE 1 Ex. 3 Ex. 4 Ex. 5 First Component THPE GE Su HEMA (g) 9.0 9.59.8 Second Component Dimethacrylated ε-caprolactone-1,4- 1.0 0.5 0.2cyclohexanedimethanol adduct (g) Initiators and Fillers Camphorquinone(g) 0.132 0.132 0.132 EDB (g) 0.132 0.132 0.132 Schott 8235 glass powder(g) 28.0 28.0 28.0 Degussa Aerosil ® OX-50 fumed silica (g) 2.0 2.0 2.0Properties Conversion %, C-peak   82%   90%   87% Shrinkage (groundfilm-Ar) %, average of 2 1.64% 1.53% 1.43% Shrinkage Stress (N) 50 49 51std dev 4 1 3 Flex Strength (MPa) 114 116 109 std dev 19 21 12 FractureToughness 2.07 2.22 2.38 [MPa (m^(0.5))] std dev 0.07 0.16 0.15

Examples 6, 7, and 8 Shrinkage of Bis-GMA/DM-CL-CHDM Composites vsBis-GMA/TEGDMA Composites

Bisphenol-A-glycidyl methacrylate adduct (“Bis-GMA”) was obtained fromEssTech (Essington, Pa.), product code X 950-0000. Triethylene glycoldimethacrylate (“TEGDMA”) was obtained from EssTech (Essington, Pa.),product code X 943-7424. DM-CL-CHDM was prepared in Example 2 above. Themonomer components, photoinitiators, and fillers were combined in the“max 40” size cup of a Flack Tek SpeedMixer™ under yellow light to avoidpremature polymerization. The contents were mixed for two 30-secondintervals at 3500 rpm. The mixture was debubbled in the vacuum oven at40° C. for 12 hrs. The resulting paste was stored in a foil-wrappedcontainer to exclude light and stored in a desiccator before use.

The composition and shrinkage of the dental composites are shown inTable 2. The shrinkage measurement by ground-film Ar method was carriedout as described above.

The results show that using DM-CL-CHDM to replace TEGDMA in thetraditional dental composite materials significantly reduced theshrinkage. The shrinkage of the Bis-GMA DM-CL-CHDM composite materialsdecreased with reduced amount of DM-CL-CHDM.

TABLE 2 Ex. 6 Ex. 7 Ex. 8 Ratio of First Component to Second 70:30 70:3090:10 Component First Component Bis-GMA (g) 3.5 3.5 4.5 Second ComponentTEGDMA (g) 1.5 0 0 DM-CL-CHDM (g) 0 1.5 0.5 Initiators and FillersCamphorquinone (g) 0.065 0.065 0.065 EDB (g) 0.065 0.065 0.065 Schott8235 glass powder (g) 14.0 14.0 14.0 Degussa Aerosil ® OX-50 fumedsilica (g) 1.0 1.0 1.0 Properties Shrinkage (ground film-Ar) %, averageof 2 3.26% 2.57% 2.27%

This experiment demonstrates that DM-CL-CHDM allows for the creation ofa composite with superior shrinkage performance relative to TEGDMA.

1. An uncured dental composite material comprising a. a composition comprising at least one compound of the formula: E¹-R¹ _(n)—O—R²-Q-R³—O—R⁴ _(m)-E² wherein: Q is selected from the group consisting of: (i) a carbocyclic ring containing 5 or 6 carbon atoms with up to 3 C₁₋₃ alkyl substituents on the ring; (ii) S—R⁵-T wherein S and T are each independently carbocyclic rings containing 5 or 6 carbon atoms with up to 3 C₁₋₃ alkyl substituents on the ring, and R⁵ is a covalent bond or an alkylene group containing 1, 2, 3 or 4 carbon atoms; and (iii) a carbocyclic fused ring system containing two fused rings containing a total of 8 to 10 carbon atoms with up to 4 C₁₋₃ alkyl substituents on the fused ring system; R² and R³ are each independently selected from the group consisting of a covalent bond and an alkylene group containing 1 to 4 carbon atoms; R¹ is a repeat unit of the formula

R⁴ is a repeat unit of the formula

E¹ and E² are each independently

wherein R⁶ is H (acryloyl) or CH₃ (methacryloyl); n and m are each independently an integer greater than 0; a is independently an integer from 3 to 6; a′ is independently an integer from 3 to 6; provided that neither R² nor R³ is a covalent bond bonded directly to an aromatic ring; and provided that the degree of polymerization of the at least one compound is between 2 and 30; b. optionally, at least one other polymerizable (meth)acrylic ester component; c. at least one polymerization initiator compound; and d. at least one filler selected from the group consisting of barium aluminum silicate, barium aluminum borosilicate, ytterbium trifluoride, glass beads, silica, quartz, borosilicates, alumina, alumina silicates, and mixtures thereof, wherein the total amount of the at least one filler is from about 40 weight percent to about 90 weight percent, based on the total weight of the uncured dental composite material.
 2. The uncured dental composite material of claim 1 wherein Q is selected from the group consisting of


3. The uncured dental composite material of claim 2 wherein Q is 1,4-cyclohexylene.
 4. The uncured dental composite material of claim 1 wherein Q is S—R⁵-T, R⁵ is 2,2-propylene or methylene, and S and T are each cyclohexylene or phenylene.
 5. The uncured dental composite material of claim 4 wherein Q is selected from the group consisting of:


6. The uncured dental composite material of claim 1 wherein Q is selected from the group consisting of


7. The uncured dental composite material of claim 1 wherein R²═R³ and R² and R³ are each a covalent bond or a methylene group.
 8. The uncured dental composite material of claim 1 wherein the degree of polymerization is between 2 and
 10. 9. The uncured dental composite material of claim 1 wherein a and a′ are both
 5. 10. The uncured dental composite material of claim 9, wherein R² and R³ are each a methylene group, Q is 1,4-cyclohexylene, R⁶ is a methyl group, and degree of polymerization is between 2 and
 6. 11. The uncured dental composite material of claim 1 further comprising at least one photoinitiating accelerator, an activator, a pigment, a radiopaquing agent, a stabilizer, and an antioxidant.
 12. A dental restoration article that is made by forming and curing the uncured dental composite material of claim
 10. 13. A composition comprising at least one compound of Formula I E¹-R¹ _(n)—O—R²-Q-R³—O—R⁴ _(m)-E²  I wherein: Q is selected from the group consisting of:

(ii) S—R⁵-T wherein S and T are each independently carbocyclic rings containing 5 or 6 carbon atoms with up to 3 C₁₋₃ alkyl substituents on the ring, and R⁵ is a covalent bond or an alkylene group containing 1, 2, 3 or 4 carbon atoms; and (iii) a carbocyclic fused ring system containing two fused rings containing a total of 8 to 10 carbon atoms with up to 4 C₁₋₃ alkyl substituents on the fused ring system; R² and R³ are each independently selected from the group consisting of a covalent bond and an alkylene group containing lto 4 carbon atoms; R¹ is a repeat unit of the formula

R⁴ is a repeat unit of the formula

E¹ and E² are each independently

wherein R⁶ is H (acryloyl) or CH₃ (methacryloyl); n and m are each independently an integer greater than 0; a is independently an integer from 3 to 6; a′ is independently an integer from 3 to 6; and provided that neither R² nor R³ is a covalent bond bonded directly to an aromatic ring; and provided that the degree of polymerization of the compound is between 2 and
 30. 14. The uncured dental composite material of claim 1, wherein the total amount of the at least one filler is from about 50 weight percent to about 85 weight percent, based on the total weight of the uncured dental composite material. 